Comparison of CYP3A4-Inducing Capacity of Enzyme-Inducing Antiepileptic Drugs Using 4beta-Hydroxycholesterol as Biomarker.
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Hole K, Wollmann BM, Nguyen C, Haslemo T, Molden E
Comparison of CYP3A4-Inducing Capacity of Enzyme-Inducing Antiepileptic Drugs Using 4beta-Hydroxycholesterol as Biomarker.
Ther Drug Monit. 2018 Aug;40(4):463-468. doi: 10.1097/FTD.0000000000000518.
- PubMed ID
- 29649093 [ View in PubMed]
- Abstract
BACKGROUND: Enzyme-inducing antiepileptic drugs (EIAEDs) are among the clinically most important inducers of cytochrome P450 (CYP) 3A4, but there is limited evidence regarding the comparative potency of each EIAED in raising CYP3A4 activity. The aim of this study was to estimate CYP3A4-inductive potency of EIAEDs by comparing CYP3A4 activity in patients treated with carbamazepine, phenobarbital, or phenytoin. METHODS: Residual serum samples from patients treated with EIAEDs or levetiracetam were collected from a therapeutic drug monitoring service for analysis of 4beta-hydroxycholesterol (4betaOHC), which is an indicator of CYP3A4 activity. The samples were collected between January and September 2016 at Diakonhjemmet Hospital, Oslo, Norway. Concentration of 4betaOHC, EIAEDs, and levetiracetam was measured by ultra-performance liquid chromatography tandem mass spectrometry. Kruskal-Wallis and Mann-Whitney tests were used for comparison of 4betaOHC levels between the subgroups. RESULTS: In total, 4betaOHC measurements for 343 and 339 patients treated with EIAEDs and levetiracetam, respectively, were included in the study. Compared with levetiracetam-treated patients, the median 4betaOHC concentration was 3.3-fold, 5.8-fold, and 6.9-fold higher in patients using phenobarbital, phenytoin, or carbamazepine, respectively (P < 0.0001). Phenytoin users (n = 65) and carbamazepine users (n = 225) had 1.8- and 2.1-fold higher median 4betaOHC concentration than phenobarbital users (n = 28), respectively (P
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Phenytoin Cytochrome P450 3A4 Protein Humans NoSubstrateInducerDetails - Drug Interactions
Drugs Interaction Integrate drug-drug
interactions in your softwareDisopyramideFosphenytoin The serum concentration of Disopyramide can be decreased when it is combined with Fosphenytoin. SaquinavirFosphenytoin The serum concentration of Saquinavir can be decreased when it is combined with Fosphenytoin. SaquinavirPhenytoin The serum concentration of Saquinavir can be decreased when it is combined with Phenytoin.